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Molecules (Basel, Switzerland) Nov 2023Polyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but...
Polyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but also facilitates the absorption of multiple drugs. Our previous study found that the long-term application of PEG400 as an adjuvant in traditional Chinese medicine preparations resulted in wasting and weight loss in animals, which aroused our concern. In this study, 16S rRNA high-throughput sequencing technology was used to analyze the diversity of gut microbiota, and LC-MS/MS Q-Exactive Orbtriap metabolomics technology was used to analyze the effect of PEG400 on the metabolome of healthy mice, combined with intestinal pathological analysis, aiming to investigate the effects of PEG400 on healthy mice. These results showed that PEG400 significantly altered the structure of gut microbiota, reduced the richness and diversity of intestinal flora, greatly increased the abundance of (), increased the proportion of Bacteroidetes to Firmicutes, and reduced the abundance of many beneficial bacteria. Moreover, PEG400 changed the characteristics of fecal metabolome in mice and induced disorders in lipid and energy metabolism, thus leading to diarrhea, weight loss, and intestinal inflammation in mice. Collectively, these findings provide new evidence for the potential effect of PEG400 ingestion on a healthy host.
Topics: Mice; Animals; Gastrointestinal Microbiome; Excipients; RNA, Ribosomal, 16S; Chromatography, Liquid; Tandem Mass Spectrometry; Metabolome; Weight Loss
PubMed: 38005284
DOI: 10.3390/molecules28227562 -
International Journal of Pharmaceutics May 2024Liposomes are widely used in the pharmaceutical industry as drug delivery systems to increase the efficacy and reduce the off-target toxicity of active pharmaceutical... (Review)
Review
Liposomes are widely used in the pharmaceutical industry as drug delivery systems to increase the efficacy and reduce the off-target toxicity of active pharmaceutical ingredients (APIs). The liposomes are more complex drug delivery systems than the traditional dosage forms, and phospholipids and cholesterol are the major structural excipients. These two excipients undergo hydrolysis and/or oxidation during liposome preparation and storage, resulting in lipids hydrolyzed products (LHPs) and cholesterol oxidation products (COPs) in the final liposomal formulations. These excipient-related impurities at elevated concentrations may affect liposome stability and exert biological functions. This review focuses on LHPs and COPs, two major categories of excipient-related impurities in the liposomal formulations, and discusses factors affecting their formation, and analytical methods to determine these excipient-related impurities.
Topics: Excipients; Liposomes; Drug Contamination; Cholesterol; Hydrolysis; Phospholipids; Oxidation-Reduction; Chemistry, Pharmaceutical; Drug Stability
PubMed: 38688429
DOI: 10.1016/j.ijpharm.2024.124164 -
Journal of Pharmaceutical Sciences Jul 2016A medicine consists of 2 fundamental parts: the active pharmaceutical ingredient and the excipient. Most, if not all, medicines could not be made without the use of... (Review)
Review
A medicine consists of 2 fundamental parts: the active pharmaceutical ingredient and the excipient. Most, if not all, medicines could not be made without the use of excipients. In the early times, the safety of excipients was overlooked and no specific safety tests were generally conducted. This fact has been changed over times and is currently being recognized that the excipient's toxicity is not negligible, because its direct interaction with the active pharmaceutical ingredient or between other excipients may occur, leading to a potential change in the relationship between effectiveness and toxicity. This review is intended to address the general status of the pharmaceutical excipients and to describe the safety assessment. As a summary, this review suggests the interest of simplifying the formulations as much as possible and the interest of reducing the number of excipients necessary to strictly meet the required functions. The risk/benefit ratio of an excipient should be always evaluated on the basis of not only its production and quality but also of its safety. Further research according to Good Manufacturing Practices, Guiding Principles in Toxicology Assessment, Good Laboratory Practices, and Good Distribution Practices requirements are needed and are fundamental for health safety, contributing to a comprehensive picture of this matter.
Topics: Chemistry, Pharmaceutical; Drug Compounding; Drug Stability; Drug-Related Side Effects and Adverse Reactions; Excipients; Humans; Safety
PubMed: 27262205
DOI: 10.1016/j.xphs.2016.03.019 -
AAPS PharmSciTech Jan 2018The choice of excipients constitutes a major part of preformulation and formulation studies during the preparation of pharmaceutical dosage forms. The physical,... (Review)
Review
The choice of excipients constitutes a major part of preformulation and formulation studies during the preparation of pharmaceutical dosage forms. The physical, mechanical, and chemical properties of excipients affect various formulation parameters, such as disintegration, dissolution, and shelf life, and significantly influence the final product. Therefore, several studies have been performed to evaluate the effect of drug-excipient interactions on the overall formulation. This article reviews the information available on the physical and chemical instabilities of excipients and their incompatibilities with the active pharmaceutical ingredient in solid oral dosage forms, during various drug-manufacturing processes. The impact of these interactions on the drug formulation process has been discussed in detail. Examples of various excipients used in solid oral dosage forms have been included to elaborate on different drug-excipient interactions.
Topics: Administration, Oral; Capsules; Drug Compounding; Drug Stability; Excipients; Tablets
PubMed: 28895106
DOI: 10.1208/s12249-017-0864-4 -
Annals of the New York Academy of... Jun 2017Cucurbit[7]uril (CB[7]), belonging to the cucurbit[n]uril family (CB[n], n = 5-8, 10, or 13-15), may form host-guest complexes with a variety of small molecules of... (Review)
Review
Cucurbit[7]uril (CB[7]), belonging to the cucurbit[n]uril family (CB[n], n = 5-8, 10, or 13-15), may form host-guest complexes with a variety of small molecules of biomedical interest. The physical and chemical properties of the complexed drugs are often improved as a result of this complexation, suggesting the potential application of CB[7] as a pharmaceutical excipient. This review has summarized the most recent research progress reported between 2011 and early 2017 regarding the biocompatibility of CB[7] and the influence of CB[7] on the stability, solubility, biouptake, and biological activities (including therapeutic efficacies and toxicities) of guest drug molecules. Through this systemic summary and analysis, we intend to stimulate further research efforts in this area and promote the use of CB[7] as an emerging pharmaceutical excipient to improve various properties of drug molecules (or active pharmaceutical ingredients).
Topics: Bridged-Ring Compounds; Drug Delivery Systems; Excipients; Humans; Imidazoles; Molecular Structure; Small Molecule Libraries
PubMed: 28692768
DOI: 10.1111/nyas.13376 -
Food and Chemical Toxicology : An... Oct 2014Transcutol® (Diethylene glycol monoethyl ether, DEGEE), CAS # 111-90-0, is commonly used as a vehicle in the formulation or manufacturing process of pharmaceuticals,... (Review)
Review
Transcutol® (Diethylene glycol monoethyl ether, DEGEE), CAS # 111-90-0, is commonly used as a vehicle in the formulation or manufacturing process of pharmaceuticals, cosmetics, and food additives. This paper presents unpublished nonclinical safety data using a form of DEGEE which includes a significantly decreased level of impurities, specifically ethylene glycol and diethylene glycol. It also reviews the history of use, regulatory status, and previously published toxicity data for DEGEE. The review supports that DEGEE is well tolerated across animal species and gender with toxicity occurring only at levels well above those intended for human use. At high levels of exposure, the kidney is identified as the critical target organ of DEGEE toxicity. DEGEE is negative for genotoxicity in in vitro and in vivo studies. Subchronic and chronic toxicity studies produced no reports of preneoplastic changes in organs, but the animal data is insufficient to allow a definitive opinion as to carcinogenicity. In silico data suggested that DEGEE is not carcinogenic or genotoxic. Developmental toxicity was seen in rats but only at levels 200 times greater than the estimated oral Permissible Daily Exposure Level of 10 mg/kg/day. The nonclinical data along with the long history of DEGEE use as a vehicle and solvent by multiple routes provide evidence of its safety. Furthermore, the novel data discussed herein provides evidence that toxicity previously associated with high levels of DEGEE in nonclinical studies conducted prior to 1990 could possibly be attributed to the presence of significant amounts of ethylene glycol or other impurities.
Topics: Animals; Carcinogenicity Tests; Consumer Product Safety; DNA Damage; Dose-Response Relationship, Drug; Ethylene Glycols; Excipients; Humans; Models, Animal; Salmonella typhimurium; Toxicity Tests, Acute; Toxicity Tests, Chronic; Toxicity Tests, Subchronic
PubMed: 25016034
DOI: 10.1016/j.fct.2014.06.028 -
Journal of Pharmaceutical Sciences Mar 2023The performance of pharmaceutical dosage forms relies heavily on the characteristics of the excipients that are incorporated into the drug product during the...
The performance of pharmaceutical dosage forms relies heavily on the characteristics of the excipients that are incorporated into the drug product during the manufacturing process. Therefore, it is imperative that formulators are able to accurately and completely specify the key chemical and physical properties of those excipients. Current approaches to describing excipients are outdated and inadequate for the needs of the 21 century and in this article we highlight the benefits of a more systematic and comprehensive approach to specifying and controlling excipient properties. We hope that this will prompt the users, suppliers, and manufacturers of excipients to take a careful look at current approaches and develop tangible proposals for attaining an enhanced future state.
Topics: Chemistry, Pharmaceutical; Excipients
PubMed: 36526004
DOI: 10.1016/j.xphs.2022.12.003 -
Molecules (Basel, Switzerland) Feb 2022β-cyclodextrin has a unique annular hollow ultrastructure that allows encapsulation of various poorly water-soluble drugs in the resulting cavity, thereby increasing...
β-cyclodextrin has a unique annular hollow ultrastructure that allows encapsulation of various poorly water-soluble drugs in the resulting cavity, thereby increasing drug stability. As a bioactive molecule, the metabolism of β-cyclodextrin is mainly completed by the flora in the colon, which can interact with API. In this study, understanding the in vivo fate of β-cyclodextrin, a LC-MS/MS method was developed to facilitate simultaneous quantitative analysis of pharmaceutical excipient β-cyclodextrin and API dextromethorphan hydrobromide. The established method had been effectively used to study the pharmacokinetics, tissue distribution, excretion, and metabolism of β-cyclodextrin after oral administration in rats. Results showed that β-cyclodextrin was almost wholly removed from rat plasma within 36 h, and high concentrations of β-cyclodextrin distributed hastily to organs with increased blood flow velocities such as the spleen, liver, and kidney after administration. The excretion of intact β-cyclodextrin to urine and feces was lower than the administration dose. It can be speculated that β-cyclodextrin metabolized to maltodextrin, which was further metabolized, absorbed, and eventually discharged in the form of CO and HO. Results proved that β-cyclodextrin, with relative low accumulation in the body, had good safety. The results will assist further study of the design and safety evaluation of adjuvant β-cyclodextrin and promote its clinical development.
Topics: Animals; Chromatography, High Pressure Liquid; Excipients; Male; Rats; Rats, Wistar; Tandem Mass Spectrometry; Tissue Distribution; beta-Cyclodextrins
PubMed: 35164401
DOI: 10.3390/molecules27031138 -
Journal of Pharmaceutical Sciences Mar 2015Pharmaceutical excipients are essential components of most modern dosage forms. Although defined as pharmacologically inert, excipients can be thought of as the true... (Review)
Review
Pharmaceutical excipients are essential components of most modern dosage forms. Although defined as pharmacologically inert, excipients can be thought of as the true enablers of drug product performance. Unintentional variability in the properties of the excipients may be unavoidable, albeit minimizable. The variability may originate from the source, the excipient-manufacturing process, or during the manufacturing of dosage forms. Excipient variability may have a range of influences on their functionality and performance in the dosage form. A better understanding of these influences on the critical quality attributes of the final product is of prime importance. Modern analytical tools provide a significant assistance in characterizing excipient variability to achieve this understanding. The principles and concepts of Quality-by-Design, process analytical technology, and design space, provide a holistic risk-based approach toward manufacture and application of excipients in pharmaceutical formulations. The International Pharmaceutical Excipients Council (IPEC) has developed guidelines for proper selection, use, and evaluation of excipients in pharmaceutical products.
Topics: Chemistry, Pharmaceutical; Dosage Forms; Excipients; Pharmaceutical Preparations; Quality Control; Technology, Pharmaceutical
PubMed: 25561249
DOI: 10.1002/jps.24299 -
Journal of Biomedical Materials... Jul 2020The use of chitosan as a pharmaceutical excipient in the ocular field is already established. Nevertheless, some aspects related to its ocular administration, such as...
The use of chitosan as a pharmaceutical excipient in the ocular field is already established. Nevertheless, some aspects related to its ocular administration, such as sterilization and excipient's pharmacokinetics, remain unclear. So, in this study, we evaluated those two relevant aspects, related to chitosan administration in eye. We used chitosan-based ocular inserts (CI) as formulation model. CI were produced by solvent/casting method and sterilized by saturated steam. Sterilization was confirmed by direct inoculation of inserts in suitable microbiological growth media. Physicochemical characterization of inserts before and after sterilization was performed. Results suggested that, although steam sterilization changed the arrangement of the matrix, the heat and the humidity did not modify the structure of the main polymeric chain. Pharmacokinetics of CI radiolabeled with technetium-99m ( Tc) was assessed by scintigraphic images and ex vivo biodistribution study, after ocular administration in male Wistar rats. Scintigraphic and images analysis and ex vivo biodistribution study showed that the insert remained mainly in the eye until 6 hr after administration and its degradation products began to migrate to the abdominal cavity after 18 hr. Together, these data represent an important step forward the manufacturing and the clinical application of CI in the ophthalmic field.
Topics: Administration, Ophthalmic; Animals; Chitosan; Drug Carriers; Excipients; Humans; Male; Rats; Sterilization; Structure-Activity Relationship; Tissue Distribution
PubMed: 31970926
DOI: 10.1002/jbm.b.34560